Search Results (11,895)

Background/Objectives: Tissue-based metabolomic readouts in IDH-wild-type glioblastoma may be strongly shaped by how tumor tissue is surgically accessed and sampled. We aimed to determine whether, and to what extent, surgical sampling context structures the HRMAS metabolic landscape, and to disentangle sampling-related contributions from clinico-anatomical confounders. Methods: We retrospectively analyzed 99 patients with de novo IDH-wild-type glioblastoma (35 biopsy-only, 64 resection: 40 gross-total, 21 near-total, 3 subtotal), yielding 166 HRMAS spectra and 47 quantified metabolites (nmol/mg). Patient-level profiles were compared using PCA, metabolite-wise testing, pathway-level aggregation (10 pathways), and variance partitioning by PERMANOVA, both unadjusted and adjusted for age, WHO PS, deep-seated location, midline involvement, multifocality, MGMT methylation, and eloquent area. Sensitivity analyses included clinico-anatomically restricted subgroups, 15 canonical metabolite ratios, and Probabilistic Quotient Normalization. Intratumoral heterogeneity was assessed in 44 multi-sampled patients. Results: Biopsy-only and resection-derived cases separated along PC1 in unsupervised PCA (62.6% variance; p < 0.001), with 42/47 metabolites differing after FDR correction. However, the surgical group explained only 2.6% of the total variance (PERMANOVA p = 0.026), and this share was no longer significant after confounder adjustment (p = 0.39). Clinico-anatomical restriction progressively attenuated the effect (42/47 → 1/47 significant metabolites). Ratio-based and PQN analyses showed a residual compositional difference beyond scaling (13/15 ratios; 16/47 metabolites). Intratumoral heterogeneity was greater in resections and preserved in an n-matched analysis (p = 0.020). Conclusions: The apparent biopsy-versus-resection metabolic difference is largely a composite signal reflecting clinico-anatomical patient selection with a smaller tissue-composition contribution. Biopsy-only and resection-derived specimens should not be pooled uncritically in tissue-based metabolomic studies of glioblastoma. Full article

Background: Liver histology remains the gold standard for assessing liver steatosis (LS); however, non-invasive methods are increasingly being explored in clinical practice. This study aimed to evaluate the agreement between magnetic resonance imaging (MRI) and liver histology in quantifying LS in patients with morbid obesity undergoing bariatric surgery (BS). Methods: This ancillary study is part of a prospective, double-blind, multicenter, randomized placebo-controlled trial investigating the effects of preoperative omega-3 polyunsaturated fatty acid supplementation on liver volume in morbidly obese patients undergoing BS. The parent trial yielded negative results, and randomization arm was retained as a covariate in all analyses. Patients underwent MRI within 2 days before surgery, followed by intraoperative wedge resection and TruCore needle liver biopsy. Agreement between MRI and histology was assessed using the intraclass correlation coefficient (ICC) and Cohen’s kappa coefficient (K) for both macro- and microvesicular steatosis. Results: Thirty-seven patients were enrolled; paired MRI and biopsy data were available for thirty-one (83.8%). Moderate and statistically significant agreement was observed between MRI and both TruCore (ICC: 0.52, p = 0.002; K: 0.42, p = 0.007) and wedge-resection (ICC: 0.53, p = 0.001; K: 0.29, p = 0.044) biopsies for macrovesicular steatosis. The MRI-derived values were systematically lower than histological estimates for macrovesicular steatosis (mean MRI: 23.4% vs. histology: 36.7–37.1%). No significant agreement was identified for microvesicular steatosis with either biopsy technique. Conclusions: In morbidly obese patients, MRI demonstrates only moderate agreement with liver histology for macrovesicular steatosis and is unreliable for microvesicular steatosis. The systematic underestimation of macrovesicular steatosis by MRI warrants caution when this modality is used as a standalone decision-making tool in this population. Further studies in larger and more heterogeneous cohorts are needed to better define the performance boundaries of MRI-derived fat-fraction measurement across the spectrum of obesity and metabolic liver disease. Full article

Introduction: Soft tissue sarcomas (STS) exhibit profound molecular heterogeneity. While recurrent gene fusions hold significant diagnostic and therapeutic value—guiding treatment selection and identifying novel molecular targets—our understanding of their broader clinical implications remains limited. Materials and Methods: We performed next-generation sequencing (NGS; FusionPlex Sarcoma v2, Archer™) and bioinformatic analysis (STAR v.2.7, Arriba) on formalin-fixed paraffin-embedded (FFPE) core needle biopsy specimens. The cohort consisted of patients enrolled in a phase II clinical trial (NCT03651375) who received preoperative chemoradiotherapy according to the UNRESARC protocol. Results: The analysed cohort comprised nine adult patients (median age 66 years; range 44–73) diagnosed with undifferentiated pleomorphic sarcoma (UPS; n = 3), malignant peripheral nerve sheath tumour (MPNST; n = 3), myxofibrosarcoma (MFS; n = 2), and leiomyosarcoma (LMS; n = 1), predominantly high-grade (G3; 5/9) and extremity-localised (6/9). Gene fusions were detected in one-third of patients (3/9), exclusively in G3 tumours. Specifically, we identified an SGSH-PRKCA fusion in MFS (thigh), a LINC01133-OGA fusion in MPNST (thorax), and a concurrent JAZF1-MYH7B (chr7:27995037 intronic-chr20:33563203 exon/splice-site, out-of-frame but preserving myosin domains) with a PRKCA-associated intergenic rearrangement (chr1, retaining C1/kinase domains) in UPS (upper back). Notably, the SGSH-PRKCA and JAZF1-MYH7B pairs have not been previously described in the literature for these STS subtypes. Fusion-positive (F1) cases showed stable radiological disease (RECIST 1.1 SD) and EORTC C/D pathological responses with 5–20% residual viable tumour, whereas fusion-negative (F0) cases showed a wider range of radiological and pathological outcomes, including partial response, progression, and stable disease. Conclusions: Our analysis suggests that broad genomic profiling may provide complementary molecular information in diagnostically challenging cases managed at specialised sarcoma centres, particularly when morphology and immunohistochemistry are insufficient. In the present series, however, the detected rearrangements did not alter systemic treatment, and the data do not support claims of prognostic, predictive, or therapeutic actionability. Full article

Background and Objectives: The aim of this study is to assess the mismatch repair (MMR) status and immunohistochemical changes in cases of recurrent endometrial cancer following primary surgery and to evaluate the impact of these changes on prognosis. Materials and Methods: Thirty-one patients diagnosed with endometrial cancer who underwent surgery and had pathologically confirmed recurrences were evaluated. Changes in MMR protein expression, estrogen receptor (ER)/progesterone receptor (PR), and p53 expression in primary surgery and recurrent tumor tissues were assessed using immunohistochemical methods. Prognostic factors influencing these parameters and survival data were investigated. Results: In the assessment of recurrent materials, there were four cases where the MLH-1&PMS-2 staining status changed from intact to loss and four cases that changed from loss to intact. No changes were observed in regard to MSH-2 &MSH-6 staining. The ratios of pMMR and dMMR following the primary surgery were 55% (n = 17) and 45% (n = 14), respectively. Four cases transitioned from pMMR to dMMR, and four cases transitioned from dMMR to pMMR. After recurrence, changes in the ER, PR, and P53 status were observed in seven, three, and three patients, respectively. Conclusions: Changes in the MMR status, receptors, and P53 were observed. It is necessary to re-evaluate prognostic parameters via biopsies in recurring cases and to adjust rescue treatments accordingly. Full article

The optimal management of patients with limited sentinel lymph node metastasis in breast cancer, particularly regarding whether to perform additional axillary surgery, continues to be an area of clinical uncertainty in routine practice. This multicenter retrospective cohort study aimed to evaluate adherence to ACOSOG Z0011 criteria and the oncological safety of omitting ALND in a Chinese population. We included 462 women with clinical stage T1–2N0 breast cancer who underwent breast-conserving surgery and were found to have 1–2 positive SLNs between January 2013 and December 2021. All patients received adjuvant radiotherapy and systemic therapy. Patients underwent either sentinel lymph node biopsy alone (SLNB; n = 274, 59.3%) or SLNB followed by ALND (n = 188, 40.7%). Propensity score matching (1:1) was applied to balance baseline characteristics, yielding 152 matched pairs. Disease-free survival (DFS) was the primary endpoint. No significant difference in DFS was observed between the SLNB alone and SLNB + ALND groups in either the overall cohort or the matched cohort. Multivariable Cox regression analysis confirmed that the type of axillary surgery was not independently associated with DFS in patients with 1–2 positive SLNs treated with breast-conserving surgery. Logistic regression analysis indicated that surgeons were more likely to perform ALND in patients with a higher SLN tumor burden; compared with micrometastasis, macrometastasis in 1–2 SLNs and a sentinel lymph node metastasis ratio greater than one-third were significantly associated with the selection of ALND. These findings suggest that omission of ALND was not associated with a statistically significant difference in DFS and provide real-world evidence supporting the applicability of Z0011-based axillary management in the Chinese population; however, given the observational design and potential for residual confounding, these results should be interpreted with caution. Full article

Background: The CD163+ macrophage is considered a key component of the tumor immune microenvironment (TIME) in osteosarcoma (OS) in relation to tumor progression and chemotherapy resistance. However, the relationship between CD163+ macrophage infiltration and the efficacy of neoadjuvant chemotherapy (NACT) in OS remains unexplored. Methods: This study collected a total of 195 biopsy samples from newly diagnosed, pretreated OS patients. The infiltration of CD163+ macrophages was evaluated using immunohistochemical (IHC) staining with anti-CD163 antibody. Additionally, multiplex fluorescence staining (CD8, CD68, CD163, and PDL1) was employed to further characterize the TIME profiles associated with different levels of CD163+ macrophage infiltration. The relationships between various clinical characteristics, survival outcomes, and CD163+ macrophage infiltration levels were also assessed. Results: CD163+ macrophages in biopsy tissues ranged from 2.25 cells/mm² to 3974.79 cells/mm² and 1.37 cells/mm² to 3027.20 cells/mm² in the training and validation cohorts respectively. Multivariate analysis identified that CD163+ macrophage density was an independent predictor for NACT response. Importantly, patients with high CD163+ macrophage infiltration exhibited poorer DFS, DMFS, and RFS than their counterparts. Conclusions: CD163+ macrophage infiltration was an independent predictor for NACT response. Patients with high CD163+ macrophage density benefited less from NACT and exhibited a more immunosuppressive TIME than low-density patients. Full article

Background: Low-dose CT scanning is a key tool in lung cancer screening, enabling the detection of clinically significant abnormalities in asymptomatic individuals and often prompting further diagnostic evaluation. Case Presentation: We describe the case of an 80-year-old man with a heavy smoking history who was found to have a new right middle lobe collapse on screening CT. Subsequent positron emission tomography-computed tomography (PET/CT) imaging demonstrated mild fluorodeoxyglucose (FDG) uptake (SUVmax 2.7), raising concern for a low-grade endobronchial malignancy versus mucoid impaction. Flexible fiberoptic bronchoscopy revealed a large exophytic endobronchial mass occluding the airway. Histopathologic examination of the biopsy sample unexpectedly revealed vegetable material, consistent with chronic foreign-body aspiration. Discussion: Unrecognized aspiration events are relatively common in elderly adults and can mimic malignancy on imaging. This case highlights an important diagnostic pitfall: inflammatory endobronchial processes, including foreign-body granulomas, can demonstrate FDG uptake and mimic malignancy. Conclusion: Clinicians should maintain a broad differential diagnosis when evaluating PET-avid endobronchial lesions, especially in elderly patients. Full article

Background/Objectives: We conducted an exploratory review of patients in our institutions who had undergone a PSMA PET/CT whilst on active surveillance, determining patient characteristics and trends. Methods: A retrospective cohort study of patients who were on active surveillance for low or favourable intermediate-risk prostate cancer and had a PSMA PET/CT done due to the presence of risk factors was performed. Risk factors that were an indication for PSMA PET/CT were: The presence of ISUP GG 2 disease, or ISUP GG1 disease with a PSA > 10 or a PI-RADS score of 4 or 5 on their MRI. Results: We identified 45 patients who underwent PSMA PET/CT whilst on active surveillance. Of these patients, 14 remained on active surveillance at the time of review, whilst 31 had progressed to definitive treatment. There was a significantly different distribution of PRIMARY scores between these two groups, although the average SUVMax was similar. In our practice, we found PSMA PET/CT to be particularly useful when performing confirmatory biopsies on patients who had normal MRI scans or were unable to go for the MRI at the time of diagnosis. Conclusions: PSMA PET/CT shows promise as a tool for active surveillance, particularly in men with risk factors for progressing to active treatment. However, our cohort was too small to draw definitive conclusions, and further research is needed. Full article

Background and Objectives: The pathogenesis of liver steatosis is associated with obesity and systemic inflammation, particularly in subjects with body mass index (BMI) above 40 kg/m² and altered serum levels of tumor necrosis factor alpha (TNF-α) and interleukin-10 (IL-10). Recent evidence suggests that disruption of the blood–brain barrier (BBB) may be associated with the development of steatosis, although limited data are available in humans. Thus, we assessed serum levels of neuron-specific enolase (NSE), transglutaminase 2 (TGM2), and glial fibrillary acidic protein (GFAP) as indirect markers of BBB dysfunction and examined their associations with steatosis severity, TNF-α and IL-10 in patients with morbid obesity. Materials and Methods: We biopsied the liver during bariatric surgery to assess steatosis by histology and serum markers by ELISA. Results: Most study subjects were women aged 38.7 ± 9.9 years with an average BMI of 42.3 ± 7.9 kg/m² and a steatosis prevalence of 78.9%. After grading steatosis as none (n = 8), mild (n = 17), moderate (n = 8), or severe (n = 5), we found no differences in sex, age, BMI, comorbidities, or laboratory variables, including liver enzymes. One-way ANOVA showed that serum IL-10 was 4-fold less in severe steatosis than in mild steatosis (p = 0.038), whereas TNF-α levels increased twice in severe steatosis compared to no steatosis (p = 0.029). NSE and GFAP serum levels, but not TGM2, increased proportionally to steatosis stage, showing differences between severe steatosis and no steatosis (p = 0.012 and p = 0.0002, respectively). Pearson correlation coefficients showed that NSE and GFAP were significantly associated with TNF-α (r = 0.600 and r = 0.402, respectively), but not with IL-10. Conclusions: Steatosis severity is significantly associated with markers of BBB disruption and systemic inflammation in patients with morbid obesity, suggesting a link between the BBB and liver steatosis. Full article

Background/Objectives: Chronic liver diseases, including metabolic dysfunction-associated steatohepatitis (MASH) and chronic viral hepatitis (CVH), are major global health concerns due to their potential progression to cirrhosis, liver failure, and hepatocellular carcinoma. Because liver biopsy, despite meeting the diagnostic gold standard, is invasive and associated with complications, non-invasive fibrosis assessment tools have been increasingly recommended in clinical practice. This study aimed to compare the diagnostic performance of several non-invasive fibrosis markers (ARR, APRI, FI, FIB-4, API, NFS, BARD) and transient elastography in detecting advanced liver fibrosis (F4) in patients with MASH and CVH. Methods: This retrospective study included 237 adult patients (77 MASH, 160 CVH) who underwent liver biopsy between 2017 and 2025 at the University Clinical Center of Serbia. CVH included chronic hepatitis B (CHB) and C (CHC). Patients were evaluated using serum fibrosis indices and TE, and results were compared to histological staging (F0–F4). ROC analysis assessed diagnostic performance. Results: Cirrhosis (F4) was more common in CVH than MASH (p < 0.001). In MASH, NFS (AUROC 0.931), FIB-4 (0.915), BARD (0.872), and APRI (0.878) showed high diagnostic accuracy for F4. In CHC, APRI (0.931), FIB-4 (0.863), and TE (0.938) had strong performance, while in CHB, TE (0.987) outperformed FIB-4 (0.821). Sensitivity and specificity varied by test and cohort, with TE consistently yielding the best results where available. Conclusions: Non-invasive methods, particularly NFS and FIB-4 for MASH and TE for CVH, effectively identify advanced fibrosis. Their application could significantly reduce the need for biopsy, especially in high-risk groups. TE demonstrated superior accuracy, but access limitations highlight the continued relevance of serum-based scores. Full article

Background and Objectives: Anemia is a frequent complication of chronic kidney disease (CKD), primarily attributed to erythropoietin deficiency. Interstitial fibrosis (IF), which disrupts the renal interstitium where erythropoietin-producing cells reside, may contribute to anemia independent of glomerular filtration rate (GFR). However, data in primary glomerulonephritis (PGN) are limited and conflicting. Materials and Methods: In this nationwide multicenter registry analysis (TSN-GOLD), 2794 adults with biopsy-proven PGN were included. Interstitial fibrosis was graded semi quantitatively (0–3). Anemia was defined according to KDIGO/WHO criteria. Multivariable logistic regression models were constructed to evaluate the independent association between IF severity and anemia, adjusting for age, sex, eGFR, log-transformed proteinuria, hypertension, diabetes mellitus, and biopsy diagnosis. Interaction between IF and eGFR was assessed. A predefined subgroup analysis was performed in patients with preserved renal function (eGFR ≥ 60 mL/min/1.73 m²). Results: Anemia was present in 34.4% of patients. Although moderate-to-severe IF was more frequent among anemic patients (p < 0.001), IF severity was not independently associated with anemia in multivariable analysis (p-trend = 0.72). Female sex and lower eGFR were independently associated with anemia. A statistically significant IF×eGFR interaction was observed (p = 0.0029), indicating effect modification across renal function levels. The model demonstrated moderate discrimination (AUC = 0.705). In patients with preserved renal function, IF severity was not associated with anemia. Conclusions: In this large multicenter cohort of PGN patients, interstitial fibrosis severity was not independently associated with anemia after adjustment for renal function and clinical covariates. These findings suggest that the association between interstitial fibrosis and anemia in PGN appears largely mediated by renal functional status rather than fibrosis severity alone. Full article

Liquid biopsy has emerged as a transformative tool in oncology, enabling minimally invasive and dynamic characterization of tumor biology. In prostate cancer, marked by high heterogeneity and frequent bone metastases, tissue biopsy is often challenging, highlighting the clinical value of circulating biomarkers. Circulating tumor DNA (ctDNA) is the most clinically advanced analyte, supporting detection of actionable alterations such as BRCA1/2 and ATM mutations, guiding targeted therapies, and enabling real-time monitoring of treatment response and resistance. Circulating tumor cells (CTCs) and extracellular vesicles (EVs) provide complementary insights into tumor biology and disease progression. However, challenges remain, including limited sensitivity in low tumor burden and biological confounders such as clonal hematopoiesis (CH), which can lead to false-positive findings. Emerging approaches, including fragmentomics and methylation profiling, offer improved tumor specificity and may help overcome these limitations. Together, these advances support the integration of liquid biopsy into clinical practice for personalized management and longitudinal monitoring in prostate cancer. Full article

Background: Acute cellular rejection (ACR) after heart transplantation remains incompletely explained despite standardized immunosuppression. Environmental exposures may contribute to residual immune activation; however, prior studies have focused primarily on air pollution rather than residential land-use composition. Objectives: To determine whether buffer-specific residential environmental composition is associated with rejection risk and whether these associations are scale-dependent and domain-specific. Methods: In this retrospective single-center cohort study, 30 heart transplant recipients contributed 267 biopsy-linked observations. Residential land-use composition was quantified within 300 m, 500 m, 700 m, and 1000 m buffers and aggregated into five domains: trees, other green surroundings, roads, water, and industrial land. Associations with ACR were evaluated using clustered logistic regression models adjusted for time since transplantation. Results: The strongest and only statistically robust associations after FDR correction were observed within the 300 m buffer. Tree-dominant (OR 1.42, 95% CI 1.22–1.65, q = 0.010) and industrial land exposure (OR 1.50, 95% CI 1.28–1.76, q = 0.010) were independently associated with increased odds of ACR. At 500 m, the association with trees persisted nominally (OR 1.39, 95% CI 1.03–1.88, p = 0.034), but did not remain significant after FDR correction, whereas water exposure showed a non-significant trend (OR 1.28, p = 0.057), which did not reach statistical significance. No associations were observed beyond 700 m across all models. Conclusions: Residential environmental composition may be associated with acute cellular rejection after heart transplantation in a scale-dependent manner, with signals confined to the immediate residential environment. Tree-dominant exposure within 300 m showed an association in clustered models; however, this finding was attenuated in mixed-effects sensitivity analyses. These results should be considered exploratory and hypothesis-generating study. Full article

Background/Objectives: Myxoid liposarcoma (MLS) is a malignant soft-tissue tumor and the second-most common subtype of liposarcoma, often occurring in the lower limbs of middle-aged patients. Case presentation: A 38-year-old male patient presented to the ultrasound outpatient clinic with a large mass in the right femoral region. It has been present for 15 years and mostly stable in size. Over the last two years, it has been slowly increasing in size, more rapidly in the previous 10 months, and has started to limit his range of motion. After multiparametric ultrasound and magnetic resonance imaging evaluation, the proposed diagnosis was myxoid liposarcoma. Following imaging workup, the patient was referred to the tertiary sarcoma center, where a biopsy was performed, and pathohistological diagnosis was low-grade myxoid liposarcoma. Contrast-enhanced computed tomography (CT) evaluation of the thorax, abdomen, and pelvis showed no signs of dissemination, and CT angiography showed no signs of vessel infiltration. Plastic surgery and vascular surgery specialists performed the extirpation of the mass with the partial resection of the adjacent sartorius muscle and the complete resection of the great saphenous vein. Subsequent pathohistological analysis of the mass and local lymph nodes showed clear surgical margins and no lymphatic or vascular invasion. The patient is currently under regular surveillance by an oncology specialist and awaiting adjuvant radiotherapy. Conclusions: A multidisciplinary approach is essential in the management of patients with MLS, as it provides a tailored, individualized assessment from diagnosis through treatment to ensure the best possible outcome. Full article

Background: Fertility preservation aims to maintain reproductive potential in patients undergoing potentially gonadotoxic treatments, increasingly relying on centralized cryobanks requiring ovarian tissue transport. Ovarian tissue cryopreservation is a widely implemented, evidence-based procedure for young women (age 18–35) with a regular ovarian reserve. The ovaries of patients are typically transported overnight to a centralized cryobank for freezing and storage, using a certified hypothermic organ preservation solution such as histidine-tryptophan-ketoglutarate (HTK) at 4–8 °C. The molecular effects of transport on ovarian tissue remain unclear. Methods: In this prospective study of 36 breast cancer patients, we compared whole-transcriptome RNA (RNA-seq) expression in 18 frozen–thawed ovarian biopsies after overnight hypothermic transport followed by slow-freezing versus 18 direct slow-freezing within ≤2 h under FertiPROTEKT-standard conditions. Results: The RNA-seq analysis identified 6 significantly upregulated genes (Bonferroni < 0.05, fold change > 1.5), including histone H2B and mitochondrial NADH dehydrogenase subunit 6 (MT-ND6). The small number of differentially expressed genes suggests only limited transcriptional changes between the two transport conditions. H2B upregulation was confirmed by qPCR, while MT-ND6 showed only moderate levels in RNA-seq but remained stable in qPCR. Immunohistochemical analysis confirmed protein presence and localization in formalin-fixed tissue from four samples, constituting, to our knowledge, the first report of MT-ND6 protein expression in human ovarian tissue. Conclusions: Overall, these results are consistent with subtle changes in chromatin organization and mitochondrial energy metabolism. Since RNA-seq revealed only modest differences in gene expression, with no appreciable up- or downregulation of apoptosis- or damage-related genes after ≤24 h, this indicates tissue stability under the studied combined conditions (transport + cryopreservation). These findings are consistent with the feasibility of the workflow under the studied conditions of centralized ovarian tissue cryobanking combined with overnight transportation and hypothermic HTK solution. Full article